Praziquantel dry suspension for mixed drinking of poultry and compound praziquantel effervescent dry suspension

Abstract

The invention belongs to the technical field of biological medicines, and discloses a praziquantel dry suspension for mixed drinking of poultry, which is prepared from the following components in parts by weight: 12-25 parts of praziquantel, 50-76 parts of a suspending aid and 12-25 parts of a dispersing agent. The invention also discloses a compound praziquantel effervescent dry suspension for mixed drinking of poultry. The compound praziquantel effervescent dry suspension is prepared from the following components in parts by weight: 0.3-0.5 part of ivermectin, 12-25 parts of praziquantel, 18-25 parts of a suspending aid, 8-14 parts of a dispersing agent, 25-35 parts of an effervescing agent acidic substance, 5.4-6.5 parts of an effervescing agent alkaline substance and 8-14 parts of a deflocculating agent. According to the compound praziquantel effervescent dry suspension prepared by compatibility of praziquantel and ivermectin, a new dosage form which is high in dispersity, uniform in absorption, quick in effect, high in bioavailability, capable of being drunk in a mixed mode and administrated in a group mode, stable in storage and good in physical state is developed, and a new scheme is provided for treatment of drug-resistant parasite infection and parasite mixed infection; and a basis is provided for development of new dosage forms and clinical application of veterinarians.

Description

Technical Field

[0001] The invention belongs to the technical field of veterinary drugs, and in particular relates to a poultry drinking praziquantel dry suspension and a compound praziquantel effervescent dry suspension. Background Art

[0002] Praziquantel is a broad-spectrum drug against trematodes and tapeworms. Since its introduction, it has been recommended as the drug of choice for the treatment of zoonotic schistosomiasis due to its low toxicity, high efficiency and broad spectrum. The mechanism of action of praziquantel mainly consists of two aspects: direct action on the worm and immune effect of the host. Praziquantel comes into contact with the worm in the host and produces an effect similar to 5-hydroxytryptamine (5-HT), causing the worm to produce spastic paralysis and fall off. It can also affect the permeability of calcium ions in the muscle cells of the worm, leading to an increase in the intracellular calcium ion content, causing the worm to paralyze and fall off; praziquantel has a direct immunomodulatory effect, which can reduce the activity of glutathione-S-transferase in the worm, causing a large amount of active oxygen to accumulate in the body, damaging the antioxidant system of the worm and causing the worm to die. Praziquantel has the characteristics of low solubility and high permeability. Its low solubility affects the absorption of the drug, resulting in low biological solubility and limiting its clinical use.

[0003] Ivermectin belongs to the class of sixteen-membered macrolide compounds and is a semi-synthetic avermectin derivative. Ivermectin can specifically bind to glutamate-gated chloride channels, increase the permeability of cell membranes to chloride ions, cause a large influx of chloride ions into cells, stimulate the body to release γ-aminobutyric acid, and cause nerve or muscle cells to hyperpolarize, paralyzing and killing parasites. Since 1987, ivermectin has been widely used in the treatment of animal and human diseases. It is often used to kill parasites inside and outside animals. It is a new type of broad-spectrum, highly effective, and low-toxic antiparasitic drug. Studies have shown that ivermectin has a strong killing effect on gastrointestinal nematodes, lung nematodes, and external parasites of cattle, sheep, horses, camels, rabbits, pigs, and poultry, and can also prevent heartworms in dogs or cats.

[0004] In recent years, due to the increase in mixed infections of various types of parasites such as nematodes, tapeworms, trematodes and external parasites and the widespread use of antiparasitic drugs in veterinary clinics, many types of parasites have developed resistance to certain specific drugs. Therefore, veterinary clinics urgently need to develop a broad-spectrum anthelmintic, low-resistance and easy-to-use compound preparation. The combined use of anthelmintics is a common method to deal with drug-resistant insects or multiple infections. Reports have shown that the compound preparation prepared by mixing ivermectin and praziquantel has a wider anti-insect spectrum and anthelmintic effect. At the same time, the combined use of ivermectin and praziquantel can produce antagonistic toxic effects, and the acute toxicity of the two drugs will be weakened when used in combination.

[0005] Dry suspension is a new dosage form derived from suspension. It is a solid preparation that mixes an insoluble or poorly soluble main drug with a suspending agent or other water-soluble auxiliary material. Before use, water can be added within a certain range to form a high-quality suspension, so that the particles are dispersed in the liquid medium to form a heterogeneous dispersion system. Dry suspension has some characteristics of suspension, such as being a thermodynamically unstable coarse dispersion system. After being dispersed with water, it should meet the quality requirements of suspension. The particles in the suspension should be evenly dispersed and should not sink quickly. They should not clump after settling and should be quickly redispersed after shaking. Dry suspension can be further divided into dry suspension and suspension granules, which are prepared from auxiliary materials such as suspending agents, wetting agents, and dispersants. Compared with suspension, dry suspension has better stability. After the drug is made into dry suspension, it has beautiful appearance, easy to use and transport, high and uniform dispersion, fast onset of action, high bioavailability, little irritation to the gastrointestinal tract and rapid absorption, which reduces the impact of individual differences on drug metabolism and reduces the occurrence of many adverse reactions. It has the characteristics of solid preparations, such as easy to carry and transport, good stability, etc., and the advantages of liquid preparations, such as fast absorption, fast onset of action, high bioavailability, and easy use. It is suitable for children, the elderly and other patients with swallowing difficulties. In veterinary clinics, it is particularly suitable for mixed drinking in large-scale chicken flocks.

[0006] At present, praziquantel tablets and praziquantel injection are used in veterinary clinics. In the prior art, Chinese patents CN116831999A and CN116942621A disclose a praziquantel tablet of pyrantel pamoate and a praziquantel tablet containing an attractant that can be eaten independently, respectively; Chinese patents CN111803443A and CN101347406A disclose a praziquantel injection and a high-content praziquantel injection, respectively. The above dosage forms are used for mixed feeding or injection. When used in mixed feed, poisoning accidents often occur due to the inability to mix evenly. Injection preparations have high injection technology requirements on the medication personnel, are labor-intensive and time-consuming, and are prone to animal stress and poisoning incidents. Summary of the invention

[0007] In order to overcome the shortcomings of existing dosage forms and parasite resistance and mixed parasite infection, the present invention provides a praziquantel dry suspension, develops a new dosage form suitable for poultry to mix and drink, can overcome the shortcomings of praziquantel's poor water solubility and inability to be administered in drinking water, provides a new solution for the treatment of drug-resistant parasitic infection and mixed parasitic infection, and has broad application prospects.

[0008] In order to achieve the above object, the present invention adopts the following technical solution: A praziquantel dry suspension for mixed drinking of poultry is prepared from the following components in parts by weight: 12 to 25 parts of praziquantel, 50 to 76 parts of suspending agents, and 12 to 25 parts of dispersants.

[0009] Preferably, the suspending agent is one or a combination of sodium carboxymethyl cellulose, hydroxymethyl cellulose, xanthan gum, guar gum, PVPK30, sodium alginate, and gelatin.

[0010] Preferably, the dispersant is one or a combination of beta-cyclodextrin, PEG6000, mannitol, and poloxamer 188.

[0011] The preparation method of the praziquantel dry suspension for poultry drinking comprises the following steps: crushing the praziquantel, suspending agent and dispersing agent, mixing them uniformly and then sieving to obtain the suspension.

[0012] The compound praziquantel effervescent dry suspension is prepared from the following components in parts by weight: 0.3-0.5 parts of ivermectin, 12-25 parts of praziquantel, 18-25 parts of suspending agents, 8-14 parts of dispersants, 25-35 parts of effervescent acidic substances, 5.4-6.5 parts of effervescent alkaline substances and 8-14 parts of deflocculating agents.

[0013] Preferably, the suspending agent is one or a combination of sodium carboxymethyl cellulose, hydroxymethyl cellulose, xanthan gum, guar gum, PVPK30, sodium alginate, and gelatin.

[0014] Preferably, the dispersant is one or a combination of beta-cyclodextrin, PEG6000, mannitol, and poloxamer 188.

[0015] Preferably, the effervescent acidic substance is one or a combination of tartaric acid, citric acid, ferulic acid, malic acid, lauric acid, fumaric acid, azelaic acid, and taurine.

[0016] Preferably, the effervescent alkaline substance is one or a combination of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, and calcium carbonate.

[0017] Preferably, the deflocculating agent is one or a combination of citrate, tartrate, phosphate, carbonate, glycinate, magnesium succinate, and sodium dehydrocholate.

[0018] The preparation method of the compound praziquantel effervescent dry suspension comprises the following steps: crushing and mixing the ivermectin, praziquantel, suspending agent, dispersant, effervescent acidic substance, effervescent alkaline substance and deflocculant uniformly and then sieving to obtain the suspension.

[0019] The beneficial effects of the present invention are: The compound praziquantel effervescent dry suspension prepared by combining praziquantel and ivermectin in the present invention has developed a new dosage form with high dispersibility, uniform absorption, rapid effect, high bioavailability, drinkability and group administration, stable storage and good physical state, provides a new solution for the treatment of drug-resistant parasitic infections and mixed parasitic infections, and provides a basis for the development of new dosage forms and veterinary clinical applications.

[0020] The invention can be directly added in proportion to an automatic drinking fountain for use, is more convenient to use, and is convenient for full-field medication in large-scale breeding farms. At the same time, it disperses quickly and evenly, has a slow sedimentation speed, is not easy to clog the drinking water line, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a diagram showing the suspension effect of the praziquantel dry suspension of Example 1 of the present invention.

[0022] Figure 2 This is a diagram showing the suspension effect of the compound praziquantel effervescent dry suspension according to Example 4 of the present invention. DETAILED DESCRIPTION

[0023] The present invention is further described in detail below in conjunction with examples and specific implementation methods.

[0024] Example 1 A praziquantel dry suspension for poultry drinking water is composed of the following main drugs and auxiliary materials: each 100g includes: main drug: 25g praziquantel, auxiliary materials: 60g hydroxypropyl methylcellulose, 15g PEG6000, and the preparation process is as follows: The first step is to accurately weigh 25 grams of praziquantel as the raw material drug; In the second step, 60 grams of suspending agent and 15 grams of dispersing agent were accurately weighed and added into a grinder. After being fully crushed and mixed evenly, sieved to obtain praziquantel dry suspension. The suspension effect was shown in FIG. Figure 1 .

[0025] Example 2 A praziquantel dry suspension for mixed drinking of poultry is composed of the following main drugs and auxiliary materials: each 100 g includes: main drug: 12 g praziquantel, auxiliary materials: 76 g sodium carboxymethyl cellulose, 12 g PEG6000, and the preparation process is the same as that of Example 1.

[0026] Example 3 A praziquantel dry suspension for mixed drinking of poultry is composed of the following main drugs and auxiliary materials: each 100 g includes: main drug: 20 g praziquantel, auxiliary materials: 65 g sodium carboxymethyl cellulose, 25 g PEG6000, and the preparation process is the same as that of Example 1.

[0027] Example 4 A compound praziquantel effervescent dry suspension for mixed drinking of poultry, which is composed of the following main drugs and auxiliary materials: each 100g includes: main drug: ivermectin 0.4g, praziquantel 20g, auxiliary materials: hydroxypropyl methylcellulose 20g, PEG600013.6g, tartaric acid 25.6g, sodium carbonate 6.4g, citrate 14g. The preparation process is as follows: In the first step, accurately weigh 20 grams of praziquantel and 0.4 grams of ivermectin as raw materials.

[0028] In the second step, 20 grams of suspending agent, 13.6 grams of dispersing agent, 25.6 grams of effervescent acidic substance, 6.4 grams of effervescent alkaline substance, and 14 grams of deflocculant are accurately weighed and added into a grinder. After being fully crushed and mixed evenly, the compound praziquantel effervescent dry suspension is obtained by sieving. The suspension effect is shown in FIG. Figure 2 .

[0029] Example 5 A poultry mixed drinking compound praziquantel effervescent dry suspension is composed of the following main drugs and auxiliary materials: each 100g includes: main drug: ivermectin 0.3g, praziquantel 25g, auxiliary materials: sodium carboxymethyl cellulose 18g, PEG6000 8g, tartaric acid 35g, sodium carbonate 5.4g, sodium tartrate 8.3g. The preparation process is the same as that of Example 4.

[0030] Example 6 A compound praziquantel effervescent dry suspension for mixed drinking of poultry, which is composed of the following main drugs and auxiliary materials: each 100g includes: main drug: ivermectin 0.5g, praziquantel 12g, auxiliary materials: sodium carboxymethyl cellulose 25g, PEG6000 14g, tartaric acid 30g, sodium carbonate 6g, sodium tartrate 12.5g. The preparation process is the same as that of Example 4.

[0031] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. With reference to the description of the present invention, other changes can be expected by those skilled in the art, and such changes should be included in the protection scope of the present invention.

Claims

1. A praziquantel dry suspension for poultry drinking, characterized in that: The invention is prepared from the following components in parts by weight: 12 to 25 parts of praziquantel, 50 to 76 parts of suspending agent and 12 to 25 parts of dispersant.

2. The praziquantel dry suspension for poultry drinking according to claim 1, characterized in that: The suspending agent is one or a combination of sodium carboxymethyl cellulose, hydroxymethyl cellulose, xanthan gum, guar gum, PVP K30, sodium alginate, and gelatin.

3. The praziquantel dry suspension for poultry drinking according to claim 1, characterized in that: The dispersant is one or a combination of beta-cyclodextrin, PEG6000, mannitol, and poloxamer 188.

4. A compound praziquantel effervescent dry suspension, characterized in that: The invention is prepared from the following components in parts by weight: 0.3-0.5 parts of ivermectin, 12-25 parts of praziquantel, 18-25 parts of suspending agent, 8-14 parts of dispersing agent, 25-35 parts of effervescent acidic substance, 5.4-6.5 parts of effervescent alkaline substance and 8-14 parts of deflocculant.

5. The compound praziquantel effervescent dry suspension according to claim 4, characterized in that: The suspending agent is one or a combination of sodium carboxymethyl cellulose, hydroxymethyl cellulose, xanthan gum, guar gum, PVP K30, sodium alginate, and gelatin.

6. The compound praziquantel effervescent dry suspension according to claim 4, characterized in that: The dispersant is one or a combination of beta-cyclodextrin, PEG6000, mannitol, and poloxamer 188.

7. The compound praziquantel effervescent dry suspension according to claim 4, characterized in that: The effervescent acidic substance is one or a combination of tartaric acid, citric acid, ferulic acid, malic acid, lauric acid, fumaric acid, azelaic acid, and taurine.

8. The compound praziquantel effervescent dry suspension according to claim 4, characterized in that: The effervescent alkaline substance is one or a combination of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and calcium carbonate.

9. The compound praziquantel effervescent dry suspension according to claim 4, characterized in that: The deflocculating agent is one or a combination of citrate, tartrate, phosphate, carbonate, glycine, magnesium succinate, and sodium dehydrocholate.

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